A Miscibility Study of p(MMA--HEMA)-Based Polymer Blends by Thermal Analysis and Solid-State NMR Relaxometry.

Ternary amorphous solid dispersions (ASDs) consist of a multicomponent carrier with the aim of improving physical stability or dissolution performance. A polymer blend as a carrier that combines a water-insoluble and a water-soluble polymer may delay the drug release rate, minimizing the risk of precipitation from the supersaturated state. Different microstructures of the ternary ASD may result in different drug release performances; hence, understanding the phase morphology of the polymer blend is crucial prior to drug incorporation.

Exploring the influence of hydrogen bond donor groups on the microstructure and intermolecular interactions of amorphous solid dispersions containing diflunisal structural analogues.

Drug-polymer intermolecular interactions, and H-bonds specifically, play an important role in the stabilization process of a compound in an amorphous solid dispersion (ASD). However, it is still difficult to predict whether or not interactions will form and what the strength of those interactions would be, based on the structure of drug and polymer. Therefore, in this study, structural analogues of diflunisal (DIF) were synthesized and incorporated in ASDs with poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA) as a stabilizing polymer.

Encapsulation of Cadmium-Free InP-based Quantum Dots in Cross-Linked Core-Shell Microparticles via Coaxial Electrospraying.

Quantum dots (QDs) are inorganic semiconductor nanocrystals capable of emitting light. The current major challenge lies in the use of heavy metals, which are known to be highly toxic to humans and pose significant environmental risks. Researchers have turned to indium (In) as a promising option for more environmentally benign QDs, specifically indium phosphide (InP).

The influence of hydrogen bonding between different crystallization tendency drugs and PVPVA on the stability of amorphous solid dispersions.

Amorphous solid dispersion (ASD) is one of the formulation strategies for drugs displaying low solubility and low oral bioavailability. In this study, high drug-loaded ASDs of drugs with different crystallization tendencies were prepared by spray drying. The aim was to investigate the influence of hydrogen bonding between the drug and the model polymer PVPVA on the physical stability of ASDs containing drugs with different crystallization tendencies.

Solidification and oral delivery of biologics to the colon- A review.

The oral delivery of biologics such as therapeutic proteins, peptides and oligonucleotides for the treatment of colon related diseases has been the focus of increasing attention over the last years. However, the major disadvantage of these macromolecules is their degradation propensity in liquid state which can lead to the undesirable and complete loss of function. Therefore, to increase the stability of the biologic and reduce their degradation propensity, formulation techniques such as solidification can be performed to obtain a stable solid dosage form for oral administration.

New insights on the effects of blend composition on the biodegradation and permeability of Inulin-Eudragit RS film coatings for colon drug delivery.

Inulin has been applied in Inulin-Eudragit RS (Inu-ERS) coatings as the component responsible for degradation by human microbiota. However, studies on how bacterial enzymes can degrade polysaccharides like inulin imbedded in water insoluble polymers like Eudragit RS are still elusive. The present work aims at elucidating the complex process of enzyme triggered biodegradation of inulin with various molecular weights in isolated films with Eudragit RS.

Encapsulation of Cadmium-Free InP/ZnSe/ZnS Quantum Dots in Poly(LMA-co-EGDMA) Microparticles via Co-flow Droplet Microfluidics.

Quantum dots (QDs) are semiconductor nanocrystals that are used in optoelectronic applications. Most modern QDs are based on toxic metals, for example Cd, and do not comply with the European Restriction of Hazardous Substances regulation of the European Union. Latest promising developments focus on safer QD alternatives based on elements from the III-V group.

Novel cationic cellulose beads for oral delivery of poorly water-soluble drugs.

Cellulose beads emerge as carriers for poorly water-soluble drugs due to their eco-friendly raw materials and favorable porous structure. However, drug dissolution may be limited by their poor swelling ability and the presence of closed pores caused by shrinkage of the pristine cellulose beads. In this study, novel cellulose beads that can swell in acidic environment were prepared by introducing ethylenediamine (EDA) on dialdehyde cellulose (DAC), thereby addressing the shrinkage and closed pore problem of cellulose beads.

The impact of applying an additional polymer coating on high drug-loaded amorphous solid dispersions layered onto pellets.

Inhibiting surface crystallization is an interesting strategy to enhance the physical stability of amorphous solid dispersions (ASDs), still preserving high drug loads. The aim of this study was to investigate the potential surface crystallization inhibitory effect of an additional polymer coating onto ASDs, comprising high drug loads of a fast crystallizing drug, layered onto pellets. For this purpose, bilayer coated pellets were generated with fluid-bed coating, of which the first layer constitutes a solid dispersion of naproxen (NAP) in poly(vinylpyrrolidone-co-vinyl acetate) (PVP-VA) in a 40:60 or 35:65 (w/w) ratio, and ethyl cellulose (EC) composes the second layer.

Evaluation of Different Thermoanalytical Methods for the Analysis of the Stability of Naproxen-Loaded Amorphous Solid Dispersions.

The aim of this research was to investigate three thermoanalytical techniques from the glass transition temperature (T) determination point of view. In addition, the examination of the correlation between the measured T values and the stability of the amorphous solid dispersions (ASDs) was also an important part of the work. The results showed that a similar tendency of the T can be observed in the case of the applied methods.

Complementarity of mDSC, DMA, and DRS Techniques in the Study of and Sub- Transitions in Amorphous Solids: PVPVA, Indomethacin, and Amorphous Solid Dispersions Based on Indomethacin/PVPVA.

Recently, glasses, a subset of amorphous solids, have gained attention in various fields, such as polymer chemistry, optical fibers, and pharmaceuticals. One of their characteristic features, the glass transition temperature () which is absent in 100% crystalline materials, influences several material properties, such as free volume, enthalpy, viscosity, thermodynamic transitions, molecular motions, physical stability, mechanical properties, etc. In addition to , there may be several other temperature-dependent transitions known as sub- transitions (or β-, γ-, and δ-relaxations) which are identified by specific analytical techniques.

Investigating the Potential of Ethyl Cellulose and a Porosity-Increasing Agent as a Carrier System for the Formulation of Amorphous Solid Dispersions.

In the present work, an insoluble polymer, i.e., ethyl cellulose (EC), was combined with the water-soluble polyvinylpyrrolidone (PVP) as a carrier system for the formulation of amorphous solid dispersions.

Gaining Insight into the Role of the Solvent during Spray Drying of Amorphous Solid Dispersions by Studying Evaporation Kinetics.

Spray drying is one of the most commonly used manufacturing techniques for amorphous solid dispersions (ASDs). During spray drying, very fast solvent evaporation is enabled by the generation of small droplets and exposure of these droplets to a heated drying gas. This fast solvent evaporation leads to an increased viscosity that enables kinetic trapping of an active pharmaceutical ingredient (API) in a polymer matrix, which is favorable for the formulation of supersaturated, kinetically stabilized ASDs.

The Value of Bead Coating in the Manufacturing of Amorphous Solid Dispersions: A Comparative Evaluation with Spray Drying.

Despite the fact that an amorphous solid dispersion (ASD)-coated pellet formulation offers potential advantages regarding the minimization of physical stability issues, there is still a lack of in-depth understanding of the bead coating process and its value in relation to spray drying. Therefore, bead coating and spray drying were both evaluated for their ability to manufacture high drug-loaded ASDs and for their ability to generate physically stable formulations. For this purpose, naproxen (NAP)-poly(vinyl-pyrrolidone-co-vinyl acetate) (PVP-VA) was selected as an interacting drug-polymer model system, whilst naproxen methyl ester (NAPME)-PVP-VA served as a non-interacting model system.

Porous soluble dialdehyde cellulose beads: A new carrier for the formulation of poorly water-soluble drugs.

Cellulose beads are porous spherical particles with promising futures for drug delivery applications. In this study, novel dialdehyde cellulose (DAC) beads are developed by periodate oxidation of pristine cellulose for oral delivery of weakly basic poorly water-soluble drugs. Diazepam and itraconazole were studied as model drugs.

The underestimated contribution of the solvent to the phase behavior of highly drug loaded amorphous solid dispersions.

In spite of the fact that spray drying is widely applied for the formulation of amorphous solid dispersions (ASDs), the influence of the solvent on the physical properties of the ASDs is still not completely understood. Therefore, the impact of organic solvents on the kinetic stabilization of drug components in a polymer matrix prepared by either film casting or spray drying was investigated. One polymer, PVPVA 64, together with one of four poorly water soluble drugs, naproxen, indomethacin, fenofibrate or diazepam, were film casted and spray dried using either methanol, ethanol, isopropanol, acetonitrile, acetone, dichloromethane or ethyl acetate.

Solvent influence on manufacturability, phase behavior and morphology of amorphous solid dispersions prepared via bead coating.

Bead coating or fluid-bed coating serves as an auspicious solvent-based amorphous solid dispersion (ASD) manufacturing technique in respect of minimization of potential physical stability issues. However, the impact of solvent selection on the bead coating process and its resulting pellet formulation is, to the best of our knowledge, never investigated before. This study therefore aims to investigate the influence of the solvent on the bead coating process itself (i.

Shedding a light on the physical stability of suspensions micronised with intensified vibratory milling; A trend observed with decreasing particle size as a function of time.

Intensified vibratory milling is a nanonisation and micronisation technology which can be used to enable the oral bioavailability of poorly soluble compounds. The generated nano- and microsuspensions entail a large surface area which enhances the compounds dissolution rate, yet this large surface area is thermodynamically unfavourable and hence spontaneous destabilisation may occur, i.e.

TEMPO-Oxidized Cellulose Beads as Potential pH-Responsive Carriers for Site-Specific Drug Delivery in the Gastrointestinal Tract.

The development of controlled drug delivery systems based on bio-renewable materials is an emerging strategy. In this work, a controlled drug delivery system based on mesoporous oxidized cellulose beads (OCBs) was successfully developed by a facile and green method. The introduction of the carboxyl groups mediated by the TEMPO(2,2,6,6-tetramethylpiperidine-1-oxyradical)/NaClO/NaClO system presents the pH-responsive ability to cellulose beads, which can retain the drug in beads at pH = 1.

Picking up good vibrations: Exploration of the intensified vibratory mill via a modern design of experiments.

The aim of this work was to strengthen the understanding of the intensified vibratory mill by unravelling the milling process in terms of the particle size reduction and heat generation via a modern design of experiments approach. Hence, the influence of five process parameters (acceleration, breaks during milling, bead size, milling time and bead-suspension ratio) was investigated via an I-optimal design. Particle size was measured via laser diffraction and the temperature of the sample after milling was computed.

Comparison of Amorphous Solid Dispersions of Spironolactone Prepared by Spray Drying and Electrospinning: The Influence of the Preparation Method on the Dissolution Properties.

This research aimed to compare two solvent-based methods for the preparation of amorphous solid dispersions (ASDs) made up of poorly soluble spironolactone and poly(vinylpyrrolidone--vinyl acetate). The same apparatus was used to produce, in continuous mode, drug-loaded electrospun (ES) and spray-dried (SD) materials from dichloromethane and ethanol-containing solutions. The main differences between the two preparation methods were the concentration of the solution and application of high voltage.

Development of a Surface Coating Technique with Predictive Value for Bead Coating in the Manufacturing of Amorphous Solid Dispersions.

The aim of this paper was to investigate whether a surface coating technique could be developed that can predict the phase behavior of amorphous solid dispersions (ASDs) coated on beads. ASDs of miconazole (MIC) and poly(vinylpyrrolidone--vinyl acetate) (PVP-VA) in methanol (MeOH) were studied as a model system. First, the low crystallization tendency of the model drug in MeOH was evaluated and confirmed.

Formulating monoclonal antibodies as powders for reconstitution at high concentration using spray-drying: Trehalose/amino acid combinations as reconstitution time reducing and stability improving formulations.

To increase their stability, therapeutic (or monoclonal) antibodies (mAbs) are often formulated as solids by using a variety of drying techniques, e.g. freeze-drying, spray-drying, or spray freeze-drying.

Unravelling the Miscibility of Poly(2-oxazoline)s: A Novel Polymer Class for the Formulation of Amorphous Solid Dispersions.

Water-soluble polymers are still the most popular carrier for the preparation of amorphous solid dispersions (ASDs). The advantage of this type of carrier is the fast drug release upon dissolution of the water-soluble polymer and thus the initial high degree of supersaturation of the poorly soluble drug. Nevertheless, the risk for precipitation due to fast drug release is a phenomenon that is frequently observed.

Advancing predictions of protein stability in the solid state.

The β-relaxation associated with the sub-glass transition temperature (T) is attributed to fast, localised molecular motions which can occur below the primary glass transition temperature (T). Consistent with T being observed well-below storage temperatures, the β-relaxation associated motions have been hypothesised to influence protein stability in the solid state and could thus impact the quality of e.g.